Do SGLT2 Inhibitors Protect the Kidneys? An Alternative Explanation.

Abstract

SGLT2 inhibitors are a family of drugs that were developed to treat diabetes mellitus. In randomized controlled trials, SGLT2 inhibitors seem to prevent kidney deterioration in patients with nephropathies, both diabetic and non-diabetic. However, in contrast to biochemical/physiological results (proteinuria and serum creatinine levels) that improve in all studies, the clinical results (all-cause mortality, cardiovascular death, need for dialysis, or renal transplant) do not consistently improve. In this article, the author would like to suggest that SGLT2 inhibitors do not, in fact, prevent the progression of renal diseases but rather alter laboratory results. This study will present a theory that gives an alternative explanation for the findings in the studies that would explain the above discrepancy between biochemical/physiological and clinical results. In general, the author claims that SGLT2 inhibitors change the kinetics of renal creatinine and microalbumin excretion but do not prevent parenchymal adverse changes in kidneys. This causes a dissociation between renal function markers (such as serum creatinine level and urinary protein) and the real kidney function. Thus, the clinical renal prognosis does not improve despite seemingly better laboratory results.